A randomized placebo-controlled polysomnographic study of eszopiclone in Japanese patients with primary insomnia

ObjectivesTo evaluate the efficacy and dose–response effect of eszopiclone on sleep latency and sleep maintenance in Japanese patients with primary insomnia.MethodsIn this randomized, double-blind, five-way crossover study, 72 patients received placebo, eszopiclone 1 mg, 2 mg, and 3 mg, and zolpidem 10 mg in random order for two consecutive nights with a washout period between treatments. Objective sleep measures from polysomnography (PSG) and subjective patient reports were collected.ResultsAll active treatments produced significant improvement in objective and subjective sleep latency compared with placebo (P < 0.05 for all comparisons); linear dose–response relationships were observed for eszopiclone. PSG-determined wake time after sleep onset (WASO), sleep efficiency, and number of awakenings (NA), and patient-reported measures of WASO, NA, sleep quality, sleep depth, and daytime functioning significantly improved following treatment with eszopiclone 2 mg and 3 mg and zolpidem 10 mg versus placebo (P < 0.05). Eszopiclone at all doses increased total sleep time and stage 2 sleep time (P < 0.001 for both comparisons), but did not alter REM or slow-wave sleep. Eszopiclone was generally well tolerated; the most frequently reported adverse event was mild dysgeusia.ConclusionsIn Japanese patients with primary insomnia, eszopiclone 2 mg and 3 mg significantly improved PSG-determined and patient-reported sleep latency and sleep maintenance relative to placebo.     

Familial Cervical Paragangliomas with Lymph Node Metastasis Expressing Somatostatin Receptor Type 2A

We report a case of familial, bilateral cervical paragangliomas (PGs) with lymph node metastasis. Patient I-1 is a 56-year-old man with a right carotid body tumor and a left vagal PG. Patient II-1 is a 29-year-old woman and the daughter of Patient I-1; she had a left carotid body tumor with regional lymph node metastasis. Histology of all the tumors showed the typical pattern of PGs, i.e., a zellballen pattern composed of chief cells positive for chromogranin A, and sustentacular cells positive for S100 protein. The Ki-67 labeling index was 1% to 3% in these PGs in both the primary and the metastatic tumors. Immunohistochemical analysis showed expression of somatostatin receptor (sstr) type 2A, but was negative for sstr type 5. Genomic mutation in succinate dehydrogenase type D was confirmed in both patients. Here, we present a case of familial PGs, and discuss the cases with special reference to pathologic diagnosis, genetics, and treatment.     

C-Peptide/Creatinine Ratio in Early Morning Urine as an Indicator of Residual B-Cell Function in Insulin-Dependent Diabetes

The C-peptide/creatinine (Cr) ratio in early morning urine was evaluated to assess B-cell function. The subjects were 12 boys and 36 girls with insulin-dependent diabetes mellitus (IDDM). The controls were 130 boys and 137 girls aged 4–15 years. There was a significant inverse correlation of this ratio with the duration of insulin therapy (r = -0.5807, P<0.01). The daily insulin dose in U/kg was significantly different among the following groups: 1.22 ± 0.31 U/kg in group 1 with undetectable C-peptide, 0.94 ± 0.37 in group 2 with a decreased ratio and 0.45 ± 0.28 in group 3 with a normal ratio. HbAl levels were 11.3 ±1.6% in group 1 and 9.2 ± 1.1% in group 3. The difference was significant. The result shows that the C-peptide/ Cr ratio in early morning urine is useful for assessing B-cell function in diabetic children.     

Intra-arterial Chemotherapy with Cisplatin Followed by Radical Radiotherapy for Locally Advanced Cervical Cancer

Locally advanced cervical cancer has a dismal prognosis, with a high local failure rate and a poor survival rate. To improve the cure rate for advanced carcinoma of the cervix, we initiated a study of intra-arterial (I-A) chemotherapy with cisplatin via the uterine artery prior to definitive radiotherapy. I-A chemotherapy via the internal iliac artery has been used to treat advanced cervical cancer; however, access by way of the uterine artery has not been tested for this purpose. Thirty-four patients with central tumor ≥5 cm in anteroposterior diameter observed on CT scans were treated with I-A chemotherapy. I-A chemotherapy consisted of unilateral catheterization of the uterine artery using 120 mg/m²cisplatin. After assessment of I-A chemotherapy, all but 3 patients were treated with a combination of whole-pelvis external irradiation and intracavitary irradiation. The 3 patients underwent external radiotherapy alone. Twenty-seven of 34 patients treated were evaluable for response to I-A chemotherapy. Eleven patients (41%) experienced a partial response. Seventy-six percent of the 34 patients treated with I-A chemotherapy followed by radiotherapy exhibited a complete response by the end of treatment. Toxicity was well tolerated and no death due to treatment occurred. The 2- and 5-year actuarial survival rates were 64 and 55%, respectively. The crude incidences of pelvic recurrence and distant metastasis observed at a median follow-up of 54 months were both 47%. This study for locally advanced cervical cancer suggests there is benefit to be derived from our I-A chemotherapy followed by radical radiotherapy.     

Combined cuff and suture technique for orthotopic whole intestinal transplantation in rats

For the purpose of immunological study on small intestinal transplantation (SIT), rat SIT models using direct suture technique widely have been used, which requires at least several months of training for microsurgery. Alternatively, a simple cuff technique for SIT has been mainly used by us, which reduces warm-ischemic time and the training period, but the entire intestinal grafts usually obtain a limited blood supply. This report describes a modification of a combined cuff and suture technique for rat SIT to aid beginning microsurgical transplantation researchers. The advantages are 1) use of only arterial suturing, making it easier for beginners, with the cuff technique applied to the more difficult vein anastomosis; 2) achievement of better arterial inflow and graft survival than when the arterial cuff technique is used; and 3) doing only partial clamping of the aorta, which improves animal survival and success of the procedure. A very high successful rate in orthotopic whole SIT was achieved even by beginners.     

Body fat accumulation is greater in rats fed a beef tallow diet than in rats fed a safflower or soybean oil diet

The effects of dietary fats , consisting of different fatty acids, on body fat accumulation and uncoupling protein (UCP) in interscapular brown adipose tissue were studied in rats. Metabolisable energy in experimental diets based on safflower oil, soybean oil or beef tallow was measured strictly (experiment 1). Male Wistar rats were then meal-fed an isoenergetic diet for 8 weeks (experiment 2). Each group of rats showed the same weight gain during the 8-week experimental period. Carcass fat content was greater in rats fed the beef tallow diet than in those fed the with the safflower or soybean oil diets, whereas the weight of abdominal adipose tissue was the same for all three dietary groups. Gene expression of UCP1 and the UCP content of the interscapular brown adipose tissue was lower in the beef tallow diet group than in the other dietary groups. A negative correlation was observed between carcass fat content and n-6 unsaturated fatty acid content in dietary fats. These results suggest that the greater body fat accumulation in rats fed the beef tallow diet results from lower expression of UCP1 mRNA and lower UCP content in brown adipose tissue. n-6 Polyunsaturated fatty acids may be the most effective fatty acids in limiting body fat.     

Ursolic acid as a trypanocidal constituent in rosemary

The MeOH extract of the leaves of rosemary (Rosmarinus officinalis L.) completely inhibited the motility of cultured epimastigotes of Trypanosoma cruzi at the concentration of 2 mg/ml after 2 h of incubation. Activity-guided fractionation of the MeOH extract has resulted in the isolation of three triterpene acids, betulinic, oleanolic and ursolic acids. Ursolic acid stopped the movement of all T. cruzi epimastigotes at the minimum concentration (MC(100)) of 40 micro g/ml (88 micro M) after 48 h of incubation. Oleanolic acid was less active (MC(100): 250 micro g/ml, 550 micro M) and betulinic acid was practically inactive.